Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disease caused by a mutation in the dystrophin gene. As a result, muscles from patients with DMD lack dystrophin, a 427 kDa protein located on the cytoplasmic surface of the plasma membrane, the sarcolemma, of muscle fibres (see, e.g., Blake D J, et al., (2002) Physiol Rev 82, 291-329). Dystrophin is required for the assembly of the dystrophin-associated glycoprotein complex that is embedded in the sarcolemma (see, e.g., Ohlendieck K & Campbell K P (1991) J Cell Biol 115, 1685-1694). The dystrophin-glycoprotein complex links the actin cytoskeleton to the basement membrane and is thought to provide mechanical stability to the sarcolemma (see, e.g., Petrof B J (2002) Am J Phys Med Rehabil 81, S162-S174). Although the exact function of dystrophin is still unknown, the pathology demonstrated by the skeletal muscles of young males that lack dystrophin is clear. Boys with DMD experience progressive muscle weakness beginning at about 2-5 years of age, are wheelchair bound by age 12, and die in their mid-twenties from respiratory, or cardiac failure (see, e.g., Hoffman E P, et al., (1987) Cell 51, 919-928).
There exists a need for new compositions and new methods for treating skeletal muscle disorders in general, as well as disorders related to dystrophic cells, tissues and subjects, and for preventing and/or correcting the underlying bases of pathogenesis in subjects with skeletal muscle disorders (e.g., generally as well as in dystrophic subjects).